Nature of the Influenza Virus

Influenza is the generic term for diseases / infections caused by the influenza virus. Influenza viruses are members of the Orthomyxoviridae family of viruses and comprise two genera: influenza A and B viruses, and influenza C virus. Influenza A, B and C viruses are distinguished on the basis of their internal nucleoprotein and matrix proteins which are specific for each viral type. Influenza A viruses are naturally able to infect a range of animal species, including humans, swine, birds, seals and horses. Influenza B viruses, however, infect only humans, while influenza C virus infects humans and swine. Influenza A viruses are further categorized into subtypes that are determined by the antigenicity of the surface glycoproteins, the hemagglutinin (H) and neuraminidase (N). The human influenza A strains currently in circulation are of the H1N1 and H3N2 subtypes. See WHO updates.

Historically, influenza A human infections have been caused by three subtypes of hemagglutinin (H1, H2 and H3) and two neuraminidase subtypes (N1 and N2); more recently human infections by the previously avian-restricted subtypes H5, H7 and H9 have been reported. A total of 16 distinct hemagglutinin and 9 neuraminidase influenza A subtypes have been identified; these are all prevalent in birds. Swine and horses, like humans, are limited to a much narrower range of subtypes.

Influenza A virions are pleiomorphic in structure, spherical examples being 80 -120nm in diameter, whilst filamentous forms may be up to 300nm in length. There are approximately 500 surface spike glycoproteins per particle (usually in the ratio of four hemagglutinins to one neuraminidase) that are embedded in a host-derived lipid bilayer membrane. Within the membrane is the transmembrane ion channel protein M2, while the structural protein M1 underlies the bilayer. Within the core of the virus, the single stranded negative sense RNA is associated with the six other viral proteins expressed from its genome: the nucleoprotein (NP), three transcriptases (PB2, PB1, and PA) and two nonstructural proteins (NS1 and NS2). The influenza virus genome comprises eight segments; a feature that enables “gene swapping” reassortment.

The influenza virus is able to evade host immune mechanisms through its propensity for “antigenic drift” and “shift”. The predominant foci of the host’s neutralizing immune response are the surface proteins of the virus: for influenza A and B these are the hemagglutinin antigen (HA) and neuraminidase antigen (NA). The hemagglutinin enables the virus to bind to host cell receptors and facilitates the entry of the virus into the cell where it will replicate. The neuraminidase protein enzymatically cleaves terminal sialic acid residues, and is believed to assist in the transport of the virus through the mucin layer of the respiratory tract as well as facilitating the budding of the progeny virus away from the host cell. Influenza C viruses, which present much less of a health-risk to humans, possess a single surface protein which combines the hemagglutinin, fusion activity and receptor destroying activity.